title: GASZ promotes germ cell derivation from embryonic stem cells.
abstract: Primordial germ cells (PGCs) are the first germ-line population that forms from the proximal epiblast of the developing embryo. Despite their biological importance, the regulatory networks whereby PGCs arise, migrate, and differentiate into gametes during embryonic development remains elusive, largely due to the limited number of germ cells in the early embryo. To elucidate the molecular mechanisms that govern early germ cell development, we utilized an in vitro differentiation model of embryonic stem cells (ESCs) and screened a series of candidate genes with specific expression in the adult reproductive organs. We discovered that gain of function of Gasz, a gene previously reported to participate in meiosis of postnatal spermatocytes, led to the most robust upregulation of PGC formation from both human and murine ESCs. In contrast, Gasz deficiency resulted in pronounced reduction of germ cells during ESC differentiation and decreased expression of MVH and DAZL in genital ridges during early embryonic development. Further analyses demonstrated that GASZ interacted with DAZL, a key germ cell regulator, to synergistically promote germ cell derivation from ESCs. Thus, our data reveal a potential role of GASZ during embryonic germ cell development and provide a powerful in vitro system for dissecting the molecular pathways in early germ cell formation during embryogenesis.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Liu
authors.forename: Nannan
authors.initials: N
authors.lastname: Tang
authors.forename: Denise R
authors.initials: DR
authors.lastname: Archambeault
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Huili
authors.initials: H
authors.lastname: Song
authors.forename: Chao
authors.initials: C
authors.lastname: Tang
authors.forename: Bei
authors.initials: B
authors.lastname: He
authors.forename: Martin M
authors.initials: MM
authors.lastname: Matzuk
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005854:Germ Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D011401:Promoter Regions, Genetic
chemical_list: C467810:ASZ1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C467809:Gasz protein, mouse